LESS COMMONLY RECOGNIZED CLINICAL FEATURES OF AMEBIASIS

Among the less commonly recognized clinical manifestations of intestinal and hepatic amebiasis are vague abdominal distress in the absence of diarrhea, symptoms like those of peptic ulcer, and symptoms of a kind that may be ascribed to psychoneurosis. Hepatic amebiasis may be confused with other diseases affecting areas above or below the right diaphragm, such as cholecystitis, viral hepatitis, pneumonia or pleurisy.Adequate therapy in every case must include a course of a drug effective against hepatic involvement (chloroquine or emetine) and a drug effective against intestinal involvement (Diodoquin, Milibis, or carbarsone). Even in the absence of positive results of stool examinations, a course of antiamebic therapy is always justified as a diagnostic and therapeutic measure.     

A case of fatal malabsorption syndrome caused by strongyloidiasis complicated with isosporiasis and human cytomegalovirus infection]

This 54-year-old Korean coal miner suffered from continuous watery diarrhea and weight loss after corticosteroid treatment (beta-methasone, 4 mg daily for 1 week) due to hip-bone fracture in January 1991. Except for the short therapy of steroid, no other histories were contributory. The malabsorption syndrome was aggravated while the case was treated under the impression of amebiasis or intestinal tuberculosis. AIDS antibody test by EIA was negative and quantitative analysis of serum immunoglobulins was in normal ranges. Nine months after the onset of symptoms, the case was diagnosed as malabsorption syndrome caused by complexed and aggravated infection by Strongyloides stercoralis, Isospora and cytomegalovirus in the small intestine, which were proved by stool examination and duodenal biopsy. His clinical course became worse even after high-dosed and prolonged albendazole treatment for strongyloidiasis with supportive fluid therapy. The patient was discharged in hopeless status in November, 1991 and died after one week at home.     

Progress towards an amebiasis vaccine

Amebiasis (infection by Entamoeba histolytica) remains a major health problem in much of the developing world. Morbidity and mortality from amebic dysentery and amebic liver abscess have persisted despite the availability of effective anti-amebic therapy, suggesting a need for alternative measures of disease control. Through the application of recombinant DNA technology, several E. histolytica antigens have now been expressed in prokaryotic systems and tested in animal models as vaccines to prevent invasive amebiasis. In this review, Sam Stanley Jr discusses why a vaccine for amebiasis may be feasible, and describes the recent development of several promising recombinant E. histolytica antigen-based parenteral and oral vaccine candidates.     

Serum zinc and copper levels in southeastern Turkish children with giardiasis or amebiasis

Alterations of serum zinc (Zn) and copper (Cu) concentrations are commonly found in patients suffering from gastrointestinal infections and with hepatic, renal, cardiovascular, and malignant diseases. In this study, the serum Zn and Cu levels in 20 children with giardiasis and in 40 children with amebiasis were evaluated. The serum Zn levels showed a significant decrease when compared to controls (p<0.001). After metronidazole therapy, a significant increase in Zn levels was observed (p<0.001). There was no significant difference in serum Cu levels between patients and controls before therapy. Before therapy, the serum Cu/Zn ratio in children with either giardiasis or amebiasis was significantly higher than that of the control group. After therapy, the Cu/Zn ratio was found to be back to normal. There were no significant differences in serum Zn levels and Cu/Zn ratios between children with and without diarrhea and there was no significant difference in children with or without failure to thrive. We concluded that Zn deficiency and elevated Cu/Zn ratio could be acute-phase responses to parasitic infections in children with giardiasis or amebiasis and that a successful treatment of the primary disorder will lead to complete recovery. Further studies are in progress to confirm the benefit of Zn supplementation during the acute phase of the disease, particularly in zinc-deficient regions of the world, such as in the case of Turkey.     

Towards the establishment of a porcine model to study human amebiasis

Background

Entamoeba histolytica is an important parasite of the human intestine. Its life cycle is monoxenous with two stages: (i) the trophozoite, growing in the intestine and (ii) the cyst corresponding to the dissemination stage. The trophozoite in the intestine can live as a commensal leading to asymptomatic infection or as a tissue invasive form producing mucosal ulcers and liver abscesses. There is no animal model mimicking the whole disease cycle. Most of the biological information on E. histolytica has been obtained from trophozoite adapted to axenic culture. The reproduction of intestinal amebiasis in an animal model is difficult while for liver amebiasis there are well-described rodent models. During this study, we worked on the assessment of pigs as a new potential model to study amebiasis.

Methodology/Principal Findings

We first co-cultured trophozoites of E. histolytica with porcine colonic fragments and observed a disruption of the mucosal architecture. Then, we showed that outbred pigs can be used to reproduce some lesions associated with human amebiasis. A detailed analysis was performed using a washed closed-jejunal loops model. In loops inoculated with virulent amebas a severe acute ulcerative jejunitis was observed with large hemorrhagic lesions 14 days post-inoculation associated with the presence of the trophozoites in the depth of the mucosa in two out four animals. Furthermore, typical large sized hepatic abscesses were observed in the liver of one animal 7 days post-injection in the portal vein and the liver parenchyma.

Conclusions

The pig model could help with simultaneously studying intestinal and extraintestinal lesion development.     

Entamoeba histolytica: the serine-rich gene polymorphism-based genetic variability of clinical isolates from Georgia

It is generally accepted that a majority of individuals infected by Entamoeba histolytica do not develop symptomatic disease. However, the parasite and the host factors contributing to the development of the disease, remain undetermined. It is also unclear why certain individuals develop extra-intestinal amebiasis without exhibiting apparent intestinal symptoms. An outbreak of amebic liver abscess in Tbilisi, Georgia in 1998-1999 suggested that the causative E. histolytica strain had an unusual propensity for extra-intestinal spread. To correlate the genetic differences with pathogenic potential of the parasite, we have examined the SREHP gene polymorphisms among Georgian E. histolytica isolates. Comparison of polymorphic patterns revealed the presence of several different genotypes of E. histolytica, thus preventing an association of a single genotype with hepatic disease, but supporting the previous finding of extensive genetic diversity among E. histolytica isolates from the same geographic origin.     

Neurotoxic effects during vidarabine therapy for herpes zoster.

Two cases of neurotoxic effects resulting from therapy with vidarabine are described. Both patients were undergoing treatment for cutaneously disseminated herpes zoster complicating therapy for solid malignant tumours. Both had normal renal function. The serum levels of hepatic enzymes were normal in one patient and slightly elevated in the other. Neurotoxicity was first manifested in both patients by the development of intention tremors that progressed to gross tremors. Obtundation, coma and death ensued in one patient and pain syndromes in the other. Vidarabine-induced neurotoxic effects, which may occur in the absence of hepatic or renal dysfunction or treatment with another drug, may be mild initially but may progress rapidly to more serious, even life-threatening, conditions. Presentation of neurotoxic effects should be considered an indication for withdrawal of vidarabine.     

Isoflurane activates intestinal sphingosine kinase to protect against bilateral nephrectomy-induced liver and intestine dysfunction

Acute kidney injury (AKI) frequently leads to systemic inflammation and extrarenal organ dysfunction. Volatile anesthetics are potent anti-inflammatory agents and protect against renal ischemia-reperfusion injury. Here, we sought to determine whether isoflurane, a commonly used volatile anesthetic, protects against AKI-induced liver and intestinal injury, the mechanisms involved in this protection, and whether this protection was independent of the degree of renal injury. Bilateral nephrectomy-induced AKI under pentobarbital sodium anesthesia led to severe hepatic and intestinal injury with periportal hepatocyte vacuolization, small intestinal necrosis, apoptosis, and proinflammatory mRNA upregulation. In contrast, isoflurane anesthesia reduced hepatic and intestinal injury after bilateral nephrectomy. Mechanistically, isoflurane anesthesia upregulated and induced small intestinal crypt sphingosine kinase-1 (SK1) as SK1 mRNA, protein, and enzyme activity increased with isoflurane treatment. Furthermore, isoflurane failed to protect mice treated with a selective SK inhibitor (SKI-II) or mice deficient in the SK1 enzyme against hepatic and intestinal dysfunction after bilateral nephrectomy, demonstrating the key role of SK1. Therefore, in addition to its potent anesthetic properties, isoflurane protects against AKI-induced liver and intestine injury via activation of small intestinal SK1 independently of the effects on the kidney. These findings may help to elucidate the cellular signaling pathways underlying volatile anesthetic-mediated hepatic and intestinal protection and result in novel clinical applications of volatile anesthetics to attenuate perioperative complications arising from AKI.     

Pleuropulmonary amebiasis

Pleuropulmonary amebiasis may be manifest without diarrhea or dysentery.In obscure lesions of the right lower lung field, one should always consider pleuropulmonary amebiasis-especially with low grade fever and moderate leukocytosis. Abscess and empyema contents should be examined promptly microscopically or kept warm to preserve the motility of the trophozoites until satisfactory examination is possible. Conservative therapy will successfully manage most cases of pleuropulmonary amebiasis. If a thorough search fails to reveal Entameba histolytica, and the diagnosis is still entertained, a medical therapeutic trial is in order.     

Strongyloidiasis associated with amebiasis and giardiaisis in an immunocompetent boy presented with acute abdomen

Strongyloides stercoralis (SS) is an intestinal nematode that is mainly endemic in tropical and subtropical regions and sporadic in temperate zones. SS infection frequently occurs in people who have hematologic malignancies, HIV infection and in individuals undergoing immunosuppressive therapy. In this study, we report a 12- year-old immunocompetent boy who was admitted to our hospital with acute abdomen. Laboratory evaluation showed strongyloidiasis, amebiasis and giardiasis. Clinical and laboratory findings immediately improved with albendazole therapy. Therefore, when diarrhea with signs of acute abdomen is observed, stool examinations should be done for enteroparasitosis. This approach will prevent misdiagnosis as acute abdomen. Complete clinical improvement is possible by medical therapy without surgical intervention.     

PLEUROPULMONARY AMEBIASIS

Pleuropulmonary amebiasis may be manifest without diarrhea or dysentery.In obscure lesions of the right lower lung field, one should always consider pleuropulmonary amebiasis—especially with low grade fever and moderate leukocytosis.Abscess and empyema contents should be examined promptly microscopically or kept warm to preserve the motility of the trophozoites until satisfactory examination is possible.Conservative therapy will successfully manage most cases of pleuropulmonary amebiasis.If a thorough search fails to reveal Entameba histolytica, and the diagnosis is still entertained, a medical therapeutic trial is in order.     

Entamoeba histolytica phagocytosis of human erythrocytes involves PATMK, a member of the transmembrane kinase family

Entamoeba histolytica is the cause of amebic colitis and liver abscess. This parasite induces apoptosis in host cells and utilizes exposed ligands such as phosphatidylserine to ingest the apoptotic corpses and invade deeper into host tissue. The purpose of this work was to identify amebic proteins involved in the recognition and ingestion of dead cells. A member of the transmembrane kinase family, phagosome-associated TMK96 (PATMK), was identified in a proteomic screen for early phagosomal proteins. Anti-peptide affinity-purified antibody produced against PATMK demonstrated that it was a type I integral membrane protein that was expressed on the trophozoite surface, and that co-localized with human erythrocytes at the site of contact. The role of PATMK in erythrophagocytosis in vitro was demonstrated by: (i) incubation of ameba with anti-PATMK antibodies; (ii) PATMK mRNA knock-down using a novel shRNA expression system; and (iii) expression of a carboxy-truncation of PATMK (PATMK(delta932)). Expression of the carboxy-truncation of PATMK(delta932) also caused a specific reduction in the ability of E. histolytica to establish infection in the intestinal model of amebiasis, however these amebae retained the ability to cause hepatic abscesses when directly injected in the liver. In conclusion, PATMK was identified as a member of the TMK family that participates in erythrophagocytosis and is uniquely required for intestinal infection.     

Candidosis of the central nervous system in children of the first year--one of the problems in nosocomial fungal infections]

CNS candidosis is a severe disease, one of the nosocomial fungal infections, with often lethal issue or invalidation of the patient. Specific signs are absent and early diagnosis is very difficult. Risk factors are the following: prematurity, candidal carriage, prolonged hospitalization, treatment with broad spectrum antibiotics and immunosupressors, artificial pulmonary ventilation. No single effective antifungal agent exists. In the case of acute fungal CNS infection the drug of choice is fluconazole (diflucan) characterized by high efficacy and CSF sanitation rate, the drug is used intravenously with possible switching off to oral form. If the pathogen is not susceptible to the drug (C. crusel, C. glabrata and C. tropicalis) amphotericin B is recommended (C. lusitaniae is not susceptible). In the case of renal or hepatic failure AmBisome may be used as less toxic form. If the case of prolonged disease antifungal drugs are used in a long-term regime, drugs combinations are also recommended. Complex therapy with granulocyte colony stimulating factor may be used if the previous regime was not effective.     

雏鸡源致病性粪肠球菌的分离鉴定及其耐药性分析

[背景]粪肠球菌(Enterococcus faecalis)是人和动物肠道正常菌群之一,也是一种条件性致病菌.近年来,粪肠球菌引起人和动物感染的报道越来越多.[目的]探明引起某养鸡场雏鸡发病死亡的病原及其致病性和有效治疗药物.[方法]结合临床症状和病理剖检,开展病原菌分离、生理生化特性检测和16S rRNA基因序列分...     

The efficacy of antibiotics in reducing morbidity and mortality from heatstroke – A systematic review

Severe hyperthermia, for example, classical heatstroke or exertional heatstroke from heatwaves or exercise respectively, or from drug ingestion or other non-infective pyrogens, is associated with a high mortality and morbidity, which may be chronic or permanent. Abolition of lipopolysaccharide, from gram-negative intestinal bacteria translocating into the systemic circulation via an intestinal wall rendered permeable from the hyperthermia, reduces the adverse effects, suggesting that antibiotics against the intestinal bacteria may have a similar effect. A systematic review searching Embase, MEDLINE and PubMed from the earliest date available until 2019 was conducted, according to PRISMA guidelines. Two papers were found which fit the criteria. In one, non-absorbable oral antibiotics were administered prior to the onset of heat stress, which reduced the cardiovascular dysfunction and rise in endotoxaemia, but animals succumbed at a lower temperature. In the second, non-absorbable oral antibiotics, in combination with a laxative and enema, given prior to the onset of heat stress, improved mortality; antibiotics administered after the heat stress did not, but the antibiotics used may have limited action against intestinal bacteria. Only two papers were found; both suggest an improvement in organ dysfunction or mortality after an episode of heat stress. No papers were found that investigate the sole use of antibiotics effective against intestinal bacteria given after the onset of heat stress, although biological plausibility suggest they warrant further research.     

Oral bioavailability and drug/carrier particulate systems

The oral route remains the preferred route of administration to ensure patient satisfaction and compliance. However, new chemical entities may exhibit low bioavailability after oral administration because of poor stability within the gastrointestinal tract, poor solubility in gastrointestinal fluids, low mucosal permeability, and/or extensive first-pass metabolism. Consequently, these new drug substances cannot be further developed using conventional oral formulations. This issue is addressed by an innovative approach based on the entrapment of drug molecules in drug/carrier assembling systems. The carrier materials are lipids, naturally occurring polymers or synthetic polymers, which are considered as nontoxic and biocompatible materials. Drug entrapment is intended to protect drug substances against degradation by gastrointestinal fluids. Fine drug/carrier particle size ensures increased drug dissolution rates. Carriers and particle supramolecular organization can be designed to enhance drug absorption through the intestinal epithelium and lymphatic transport. Promising preclinical results have been obtained with model drugs like paclitaxel, insulin, calcitonin, or cyclosporin. Attention has focused on mucoadhesive carriers like chitosan that favor an intimate and extended contact between drugs and intestinal cells, thus enhancing absorption. Addition of ligands such as lectins improves intestinal drug absorption through specific binding of the carrier to intestinal cell carbohydrates. In conclusion, drug/carrier particulate systems are an attractive and exciting drug delivery strategy for highly potent drug substances unsuitable for oral use. Further evidence will determine whether this approach has marked therapeutic benefits over conventional drug formulations and is compatible with large-scale industrial production and stringent registration requirements. Producing highly effective particulate systems requiring low-complexity manufacturing processes is therefore an ongoing challenge.     

微生态调节剂在慢性重型肝炎患者的治疗作用

目的探讨微生态调节剂整肠生和乳果糖在慢性重型肝炎的治疗作用。方法 162例慢性重型肝炎患者被随机分为治疗组(84例)和对照组(78例)。对照组给予常规的综合治疗,治疗组在对照组的基础上给予整肠生胶囊4粒、乳果糖口服液10 ml每日3次口服,疗程为4周。比较2组病例治疗后主要症状和体征、肝功能、凝血功能、内毒素、血氨、并发症发生率及病死率。结果与对照组比较,治疗组更有效地改善患者临床症状、肝功能及凝血功能,降低血浆内毒素、血氨浓度,减少自发性腹膜炎(SBP)、肝性脑病(HE)和肝肾综合征(HRS)等并发症发生率和患者病死率。结论微生态制通过调整肠道失调菌群,能改善患者肝功能和凝血功能,降低血氨和内毒素血症,减少并发症和病死率,对慢性重型肝炎有明显治疗作用。     

Macrophage specific drug delivery in experimental leishmaniasis

Macrophage-specific delivery systems are the subject of much interest nowadays, because of the fact that macrophages act as host cells for many parasites and bacteria, which give rise to outbreak of so many deadly diseases(eg. leishmaniasis, tuberculosis etc.) in humans. To combat these deadly diseases initially macrophage specific liposomal delivery system were thought of and tested in vivo against experimental leishmaniasis in hamsters using a series of indigenous or synthetic antileishmanial compounds and the results were critically discussed. In vitro testing was also done against macrophages infected with Leishmania donovani, the causative agent for visceral leishmaniasis. The common problem of liposome therapy being their larger size, stability and storage, non-ionic surfactant vesicles, niosomes were prepared, for their different drug distribution and release characteristics compared to liposomes. When tested in vivo, the retention capacity of niosomes was found to be higher than that of liposomes due to the absence of lipid molecules and their smaller size. Thus the therapeutic efficacy of certain antileishmanial compounds was found to be better than that in the liposomal form. The niosomes, being cheaper, less toxic, biodegradable and non-immunogenic, were considered for sometime as suitable alternatives to liposomes as drug carriers. Besides the advent of other classical drugs carriers(e.g. neoglycoproteins), the biggest challenge came from polymeric delivery vehicles, specially the polymeric nanoparticles which were made of cost effective biodegradable polymers and different natural polymers. Because of very small size and highly stable nature, use of nanoparticles as effective drug carriers has been explored in experimental leishmaniasis using a series of antileishmanial compounds, both of indigenous and synthetic origin. The feasibility of application in vivo, when tested for biological as well as for other physicochemical parameters, the polymeric nanoparticles have turned out to be the best and thus may be projected for effective use in the clinics.